The objective of this research is to broaden our understanding of mammalian genetics through the formal genetic analysis of the mouse. The major focus of the research is on the development and use of recombinant inbred (RI) mouse strains for the analysis of both traits. These RI strains are widely used by other investigators for mapping polymorphic loci and for analyzing complex traits such as resistance to microbial challenge. DNA restriction fragment variants associated with selected genes will be identified and mapped using these strains. As more markers are typed in the system the RI sets become an increasingly powerful genetic tool. By mapping selected genes through these DNA variants it may be possible to identify mouse mutations at the probe loci. This approach has led to the discovery of close linkage between one such mutation, called congenital goiter, and the gene encoding thyroglobulin. The molecular basis for this mutation will be examined by the analysis of the thyroglobulin gene, mRNA, and protein in mutant and normal mice. In addition, the feasibility of deletion mapping the murine genome using DNA markers will be tested.